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Query: UMLS:C0009402 (colorectal cancer)
 53,228 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Based on three colorectal cancer cell lines with specified K-ras status, a sensitive PCR-RFLP assay was established detecting one K-ras mutant among 106 wild-type cells. Using this assay for tissues of 124 colorectal cancer patients, 59 tumor (46%) and 11 mucosa samples (9%) were found to harbor a K-ras mutation. When using the same scalpel for collecting tumor and mucosa tissues (group A), 18% of the patients had a matching K-ras mutation in both tissues, but this coincidence was seen in 3% of patients only, when separate scalpels were used (group B). Thus we conclude that the sampling technique used for collecting specimens is a major contributor to the detection of K-ras mutations in normal appearing mucosa when a highly sensitive detection technique is used.
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PMID:Sampling technique influences the detection of K-ras mutations in normal appearing mucosa of colorectal cancer patients. 1040 53

Hypermethylation in the promoter region of the p16 gene was suspected to be involved in the tumorigenesis of colorectal cancers, although its clinical and biological significance remains obscure. In this study, we collected 84 T3N0M0 stage primary colorectal cancers that were curatively resected. The clinicopathologic data were reviewed. p16 hypermethylation was determined by a methylation-specific polymerase chain reaction (PCR). p53 overexpression was detected by immunocytochemistry (ICC). The point mutations in the 12 and 13 codons of the K-ras gene were screened by restriction enzyme analysis. Loss of heterozygosity (LOH) of the DCC (Deleted in Colorectal cancer) gene was examined by PCR using primers of the DCC (18q21) microsatellite marker. The DNA replication error (RER) was examined using 7 microsatellite markers at distinct chromosomal loci. p16 hypermethylation, regarded as an indication of p16 inactivation, was evident in 24 (28.6%) of the tumors. No correlation was found between p16 hypermethylation and various clinicopathologic factors, includinig age, sex, tumor location, tumor size, growth pattern, tumor differentiation, mucin production, vascular and/or lymphatic invasion, lymphocyte infiltration of the tumor, and serum level of carcinoembryonic antigen. There was no association between p16 hypermethylation of K-ras gene mutation, p53 overexpression and LOH of the DCC gene. However, p16 hypermethylation was significantly associated with DNA RER (p = 0.01). Survival analysis revealed a significant survival disadvantage of p16-hypermethylated versus non-p16-hypermethylated tumors (p = 0.0001). These findings indicate that p16 hypermethylation plays a role in the carcinogenesis of a subset of colorectal cancers; and the presence of p16 hypermethylation predicts shorter survival in T3N0M0 stage colorectal cancers.
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PMID:Hypermethylation of the p16 gene in sporadic T3N0M0 stage colorectal cancers: association with DNA replication error and shorter survival. 1046 Oct 63

Disseminated disease, especially to the liver, constitutes the major risk of recurrence for colorectal cancer patients. However, successful resection can still be achieved in 25-35% of colorectal cancer patients with isolated metastases. To evaluate the clinical value of occult micrometastatic disease detection in lymph nodes, we tested genetic (K-ras and p53 gene mutations) and epigenetic (p16 promoter hypermethylation) molecular markers in the perihepatic lymph nodes from colorectal cancer patients with isolated liver metastases. DNA was extracted from 21 paraffin-embedded liver metastases and 80 lymph nodes from 21 colorectal cancer patients. K-ras and p53 gene mutations were identified in DNA from liver metastases by PCR amplification followed by cycle sequencing. A sensitive oligonucleotide-mediated mismatch ligation assay was used to search for the presence of K-ras and p53 mutations to detect occult disease in 68 lymph nodes from tumors positive for these gene mutations. Promoter hypermethylation at the p16 tumor suppressor gene was examined in both liver lesions and lymph nodes by methylation-specific PCR. Sixteen of the 21 (76%) liver metastases harbored either gene point mutations or p16 promoter hypermethylation. Twelve of the 68 lymph nodes were positive for tumor cells by molecular evaluation and negative for tumor cells by histopathology and cytokeratin immunohistochemistry, whereas none were positive for tumor cells by histopathology or negative for tumor cells by molecular analysis (P = 0.0005, McNemar's test). Moreover, in three patients with lymph nodes that were histologically negative at all sites, molecular screening detected tumor DNA at one or more lymph nodes. Survival analysis showed a median survival of 1056 days for patients without evidence of lymph node involvement by molecular analysis and 165 days for patients with positive lymph nodes by this approach (P = 0.0005). These results indicate that lymph node metastasis screening in colorectal cancer patients by molecular-based techniques increases the sensitivity of tumor cell detection and can be a good predictor of recurrence in colorectal cancer patients with resectable liver metastases.
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PMID:Molecular detection of neoplastic cells in lymph nodes of metastatic colorectal cancer patients predicts recurrence. 1049 18

Both genetic and epigenetic factors contribute to the development of colorectal cancer. Specific genetic changes in proto-oncogenes, tumor suppressor genes, and DNA mismatch repair genes have led to a genetic model of colorectal tumorigenesis. Recent data highlight the importance of the TGF-beta signaling pathway in regulating the progression of colorectal cancer. The loss of the tumor suppressor activity of this pathway as well as the potentially cooperative genetic aberrations involving APC, K-ras, and p53 are reviewed in the context of the multi-step adenoma-carcinoma sequence that characterizes the development of colorectal tumorigenesis. In addition, contributing epigenetic factors including age, diet, angiogenesis, and immune response are also discussed. Combining our knowledge of the genetic and epigenetic events implicated in this disease may allow a broader understanding of the pathogenesis of colorectal cancer and hence the design of better anti-tumor interventions.
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PMID:Genetic and epigenetic contributions to colorectal cancer. 1051 22

Cell cycle variations and DNA aneuploidy, were investigated in different phases of azoxymethane (AOM)-induced colon carcinogenesis in rats by flow cytometry. K-ras gene mutations (transitions Gright curved arrow A) were frequently detected in aberrant crypt foci (ACF) initial pre-neoplastic lesions. The fraction of cells in the G2M-phase of the cell cycle was higher in ACF compared to the normal mucosa of control rats. A similar modification of the cell cycle was found in adenomas and adenocarcinomas but, unexpectedly, also in morphologically normal mucosa from AOM-treated animals indicating that AOM treatment permanently modifies cell cycle control in rat colon mucosa. These alterations, however, were not associated with DNA aneuploidy as reported in human sporadic colorectal cancer, suggesting that tumour development in AOM-treated rats is less dependent on aneuploidy.
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PMID:Cell cycle variations in azoxymethane-induced rat colorectal carcinogenesis studied by flow cytometry. 1052 22

Postoperative survival of colorectal cancer patients is often delineated by metastases spreading to the liver. Current clinical diagnostic procedures are unable to discover micrometastases in this organ. Our aim was to develop a diagnostic tool for detecting micrometastases that are present at the time of surgery. Therefore, a PCR-RFLP assay was set up tracking point mutations of the K-ras oncogene at codons 12 and 13, based on mismatch primers and restriction enzymes BstXI and XcmI. The detection limit of this assay was one mutant in one million wild-type cells. One hundred forty-two patients with colorectal carcinoma were screened for these mutations in tissue samples from their tumor, proximally adjacent mucosa, and liver. Of these, 67 patients (46%) were positive for a K-ras mutation, of which 58 had codon 12 and 9 had codon 13 mutations. No patient without a K-ras-positive tumor showed a mutation in mucosa, but 11 patients with a K-ras-positive tumor (11 of 58; 19%) were found to bear a K-ras mutation in their mucosa, and in 21 patients (21 of 64; 33%), a K-ras mutation was detected in liver tissue. Sequencing of all mutated samples revealed a 92% confirmation of PCR-RFLP results. In summary, the assay is a useful tool for detecting K-ras codon 12 and 13 mutations and allows early proof of molecular determinants of liver metastases. Such knowledge will improve the staging of colorectal cancer patients and could beneficially influence their prognosis if followed by an effective therapy.
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PMID:Sensitive detection of K-ras mutations augments diagnosis of colorectal cancer metastases in the liver. 1053 93

Familial colorectal cancer (CRC) is a major public health problem by virtue of its relatively high frequency. Some 15-20% of all CRCs are familial. Among these, familial adenomatous polyposis (FAP), caused by germline mutations in the APC gene, accounts for less than 1%. Hereditary non-polyposis colorectal cancer (HNPCC), also called Lynch syndrome, accounts for approximately 5-8% of all CRC patients. Among these, some 3% are mutation positive, that is, caused by germline mutations in the DNA mismatch repair genes that have so far been implicated (MLH1, MSH2, MSH6, PMS1, and PMS2). Most of the remaining patients belonging to HNPCC or HNPCC-like families are still molecularly unexplained. Among the remaining familial CRCs, a large proportion is probably caused by gene mutations and polymorphisms of low penetrance, of which the I1307K polymorphism in the APC gene is a prime example. Molecular genetic findings have enabled hereditary CRC to be divided into two groups: (1) tumours that show microsatellite instability (MSI), occur more frequently in the right colon, have diploid DNA, harbour characteristic mutations such as transforming growth factor beta type II receptor and BAX, and behave indolently, of which HNPCC is an example; and (2) tumours with chromosomal instability (CIN), which tend to be left sided, show aneuploid DNA, harbour characteristic mutations such as K-ras, APC, and p53, and behave aggressively, of which FAP is an example. This review focuses most heavily on the clinical features, pathology, molecular genetics, surveillance, and management including prophylactic surgery in HNPCC. Because of the difficulty in diagnosing HNPCC, a detailed differential diagnosis of the several hereditary CRC variants is provided. The extant genetic and phenotypic heterogeneity in CRC leads to the conclusion that it is no longer appropriate to discuss the genetics of CRC without defining the specific hereditary CRC syndrome of concern. Therefore, it is important to ascertain cancer of all anatomical sites, as well as non-cancer phenotypic stigmata (such as the perioral and mucosal pigmentations in Peutz-Jeghers syndrome), when taking a family cancer history.
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PMID:Genetic susceptibility to non-polyposis colorectal cancer. 1054 23

The identification of several types of familial colorectal cancer has led to the discovery of some of the genes involved in these diseases. It was subsequently shown that somatic mutations of these genes (APC, mismatch repair genes, TP53) also occur in sporadic colorectal cancer. Gradually, this molecular information is being incorporated into the standard histopathological analysis of colorectal cancer and can be used for the characterization of primary tumors. Although attempts have been made to use molecular parameters to better define dysplasia grades, differentiate between adenoma and carcinoma, and subtype carcinomas, histological parameters remain the standard for the classification of primary tumors. Nonetheless, molecular parameters may help define subgroups of colorectal carcinoma differing in prognosis and requiring individualized treatment regimens. Interesting possibilities are predicting the response of chemotherapy or radiotherapy at a molecular level and the search for metastasis by looking for molecular markers in lymph nodes or circulating blood. Other pathological tests being developed include the detection of K-ras, TP53 or APC mutations in stool and plasma. Such approaches will have a significant impact on the clinical management of colorectal cancer.
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PMID:[Molecular pathology of colorectal cancer]. 1058 88

Detection of molecular features such as K-ras mutations has been used to evaluate potential tumour markers in a wide variety of clinical samples. Here we have applied a recently developed highly sensitive method for detection of K-ras codon 12 mutations to colorectal and pancreatic cancer diagnosis. We analysed 67 faecal samples from patients undergoing diagnostic colonoscopy under suspicion of colorectal cancer. PCR products were obtained in 62 of 67 (93%) faecal samples. Mutations were detected in exfoliated cells in 6 of 22 (27%) of the adenomas and in 6 of 11 (55%) of adenocarcinomas. No false positives were observed. Agreement between faecal samples and corresponding tissues was 100% for adenocarcinomas and 65% for adenomas. Mutations were also analysed in 61 pancreatic fine-needle aspirates. Mutations were detected in 36 of 45 (80%) of the pancreatic aspirates diagnosed as pancreatic cancer without false positives. Our findings suggest that, when colorectal cancer is suspected, detection of K-ras codon 12 mutations in faecal samples using this new method is specific for colorectal tumours. Additionally, this technique is a good alternative for evaluation of pancreatic masses.
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PMID:A highly sensitive method for K-ras mutation detection is useful in diagnosis of gastrointestinal cancer. 1058 86

The mutations of K-ras gene have been demonstrated at frequencies of about 40% in human colorectal cancer. We applied a developed PCR-preferential homoduplex formation assay (PCR-PHFA) to detect a point mutation of K-ras gene in the surgical specimens from thirty patients with colorectal cancer. This method is based on the strand competition during hybridization between a double labeled amplicon, prepared from biotin and DNP labeled primers, and an unlabeled amplicon. The procedure of this method is simple and speedy, and suitable to detect mutations in a small number of samples. By using this method, the mutations were found in 37% (11/30) and confirmed by sequencing analysis. The results suggest that the PCR-PHFA system may be useful for detecting low frequent mutation of K-ras gene even in the case of an early cancer.
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PMID:[Detection of K-ras mutations in colon cancer by PHA-PHFA (preferential homoduplex formation assay)]. 1059 Jun 84


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